Metabolic Physiological Networks: The Impact of Age

Frontiers in Physiology

卷:11

Lizbeth de la Cruz²  Adriana Robles-Cabrera³  Jonathan F. Easton³  Ana Leonor Rivera³  Christopher R. Stephens³  Antonio Barajas-Martínez⁴  Ricardo Martínez-Tapia⁴ 

[1] Centro de Ciencias de la Complejidad, Universidad Nacional Autónoma de México, Mexico City, Mexico;

[2] Department of Physiology, School of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico;

[3] Instituto de Ciencias Nucleares, Universidad Nacional Autónoma de México, Mexico City, Mexico;

[4] Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico;

关键词: metabolic syndrome;    physiological networks;    systems biology;    biomarkers;    aging;   

DOI  :  10.3389/fphys.2020.587994

来源: DOAJ

【 摘 要 】

Metabolic homeostasis emerges from the interplay between several feedback systems that regulate the physiological variables related to energy expenditure and energy availability, maintaining them within a certain range. Although it is well known how each individual physiological system functions, there is little research focused on how the integration and adjustment of multiple systems results in the generation of metabolic health. The aim here was to generate an integrative model of metabolism, seen as a physiological network, and study how it changes across the human lifespan. We used data from a transverse, community-based study of an ethnically and educationally diverse sample of 2572 adults. Each participant answered an extensive questionnaire and underwent anthropometric measurements (height, weight, and waist), fasting blood tests (glucose, HbA1c, basal insulin, cholesterol HDL, LDL, triglycerides, uric acid, urea, and creatinine), along with vital signs (axillar temperature, systolic, and diastolic blood pressure). The sample was divided into 6 groups of increasing age, beginning with less than 25 years and increasing by decades up to more than 65 years. In order to model metabolic homeostasis as a network, we used these 15 physiological variables as nodes and modeled the links between them, either as a continuous association of those variables, or as a dichotomic association of their corresponding pathological states. Weight and overweight emerged as the most influential nodes in both types of networks, while high betweenness parameters, such as triglycerides, uric acid and insulin, were shown to act as gatekeepers between the affected physiological systems. As age increases, the loss of metabolic homeostasis is revealed by changes in the network’s topology that reflect changes in the system−wide interactions that, in turn, expose underlying health stages. Hence, specific structural properties of the network, such as weighted transitivity, i.e., the density of triangles in the network, can provide topological indicators of health that assess the whole state of the system. Overall, our findings show the importance of visualizing health as a network of organs and/or systems, and highlight the importance of triglycerides, insulin, uric acid and glucose as key biomarkers in the prevention of the development of metabolic disorders.

【 授权许可】

Unknown